Enigma-Mdm2 interaction and uses thereof

Abstract

The present invention relates to Enigma (PDLIM7)-Mdm2 interaction and use thereof. More particularly, it may induce an effective apoptosis of cancer cells by inhibition of an Enigma expression or an Enigma activity which induces Mdm2 destabilization and p53 activity; it may assess the prognosis of anti-cancer therapy by determining that Enigma, which is induced by SRF, is overexpressed in cancer tissues with Mdm2; it may screen anti-cancer activity substances by selecting a factor to inhibit specific binding between Enigma and Mdm2. Enigma-Mdm2 interaction and Enigma expression regulation may be utilized usefully for preventing cancers and developing therapeutic methods and anti-cancer agents.

What is claimed is: 
     
       1. A method of screening candidate substances for an anti-cancer agent, the method comprising:
 1) contacting PDZ and LIM domain 7 (PDLIM7) and Mdm2 in the presence or absence of a candidate substance, wherein the candidate substance is a peptide, a protein, an antibody, a small molecule, or a natural substance; 
 2) measuring a binding level for PDLIM7 and Mdm2; and 
 3) selecting a candidate substance that decreases the binding level for PDLIM7 and Mdm2, compared to in the absence of the candidate substance, thereby identifying an anti-cancer agent, wherein the cancer is liver cancer, stomach cancer, or colorectal cancer. 
 
     
     
       2. A method of screening candidate substances for an anti-cancer agent, the method comprising:
 1) bringing cells expressing PDZ and LIM domain 7 (PDLIM7) and Mdm2 into contact with a candidate substance; 
 2) measuring a binding level for PDLIM7 and Mdm2; and 
 3) selecting a candidate substance that decreases the binding level for PDLIM7 and Mdm2, compared to a control group untreated with the candidate substance, thereby identifying an anti-cancer agent, wherein the cancer is liver cancer, stomach cancer, or colon cancer. 
 
     
     
       3. A method of screening candidate substances for an anti-cancer agent, the method comprising:
 1) treating cells expressing PDZ and LIM domain 7 (PDLIM7) and Mdm2 with a candidate substance, wherein the candidate substance is a peptide, a protein, or an antibody; 
 2) measuring a level of PDLIM7 or Mdm2 protein; and 
 3) selecting a candidate substance that decreases stability of PDLIM7 or Mdm2 protein, compared to a control group untreated with the candidate substance, thereby identifying an anti-cancer agent, wherein the cancer is liver cancer, stomach cancer, or colon cancer. 
 
     
     
       4. The method of  claim 3 , wherein:
 the cells expressing PDLIM7 and Mdm2 also express Serum Response Factor (SRF) and 
 wherein the candidate substance further decreases stability of SRF, compared to a control group untreated with the candidate substance.